This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic lung diseases such as COPD result in exercise limitation. There is increasing evidence of systemic contributions to such limitation over and above those of the central failed organ (the lung), but the potential mechanisms remain to be elucidated. Using biopsy samples from patients with COPD, expression of skeletal muscle angiogenic regulators and inflammatory molecules will be examined as a function of muscle phenotype (normal or cachectic), controlling for other major phenotypic differences (age, disease severity, comorbidities and physical activity). The focus will continue to be on angiogenic function in general and Vascular Endothelial Growth Factor (VEGF) in particular. We will seek to identify whether abnormalities in the muscle angiogenic response to exercise are a consequence of systemic inflammation stemming from lung damage, or are based on O2 transport limitation.